The importance of detailed knowledge of craniofacial growth has been recognized for decades. Craniofacial anomalies are among the most common congenital defects. Additionally, the prevalence of orthodontic treatment exceeds 30% according to national averages. The clinical significance of this region is not restricted to physical health as even small variations in anatomy may significantly impact feelings of self- worth. Fortunately, many craniofacial disorders can be successfully treated during childhood with surgical approaches or orthodontic applications. The success of these treatments can be maximized through a comprehensive understanding of the general patterns of craniofacial growth. The goal of the proposed research project is to precisely characterize ontogenetic trajectories across the functional/developmental components of the craniofacial complex throughout childhood and into young adulthood. This project will result in a web-based application, useful for both clinicians and basic researchers, which will provide sex- and age-specific benchmarks for the normative range of craniofacial growth and development. The proposed study will leverage the considerable resources created by the NIDCR-funded project Genetic Architecture of the Human Craniofacial Complex: (R01DE016692; R.J. Sherwood, P.I.). That project collected craniofacial phenotypes from over 9,000 radiographs available as part of the Fels Longitudinal Study, the world's longest study of human growth and development. The proposed research will analyze measurements from the 6,861 of these radiographs taken from the ages of 1 month to 25 years on 779 individuals, each with from 1 to 30 radiographs over the specified age range. We will use this rich longitudinal data source to thoroughly characterize the growth trajectories of a comprehensive set of 74 craniofacial phenotypes representing basicranial, splanchnocranial, neurocranial, mixed component, and soft tissue traits. Statistical modeling of each trajectory will be accomplished using linear and non-linear mixed models, providing a detailed analysis of the population-average trajectory, the magnitude of variation in individual-level trajectories, and an assessment of secular trends. For diagnostic and prognostic purposes, we will use quantile regression to produce population percentile reference standards relative to both chronological and skeletal age, individualized reference percentiles given a past measurement, and prediction of future growth percentiles given a current measurement. Finally, these clinically useful tools will be made accessible via a web-based application. PUBLIC HEALTH RELEVANCE: In terms of public health, the proposed research is particularly relevant and timely. The goal of the proposed study is a detailed characterization of craniofacial growth using state-of-the-art longitudinal modeling. Deformities of the craniofacial region are among the most common congenital defects with effects ranging from minor aesthetic issues to deformities with significant health outcomes. The results of the proposed research, made available via a web-based application, will help to improve the ability to predict specific outcomes, and will provide important information for optimizing timing and duration of treatment regimens.